The Clinical Significance of Crohn Disease Activity at Resection Margins Sasan Setoodeh, MD; Li Liu, MD, PhD; Sarag A. Boukhar, MBChB; Amit G. Singal, MD, MS; Maria Westerhoff, MD; Akbar K. Waljee, MD, MS; Tasneem Ahmed, DO; Purva Gopal, MD, MS  Context.—Conflicting data about the clinical signifi- cance of microscopic Crohn disease (CD) activity at resection margins have led to varying practice patterns for routine reporting by pathologists. Objective.—To characterize the association between active disease at resection margins with postoperative CD recurrence and time-to-recurrence in the era of anti–tumor necrosis factor therapy. Design.—We performed a multicenter retrospective cohort study of 101 consecutive CD bowel resections during 10 years. Margin slides were reviewed, and CD activity at the margins was graded as none, mild, moderate, or severe. The association between microscopic CD activity at the margin with postoperative recurrence and time-to-recurrence were evaluated with logistic regression and Cox regression analyses, respectively. Results.—Crohn disease activity at resection margins was reported in 43% of pathology reports. Resection margins had CD involvement in 39.6% of cases, 20 of which were classified as mild, 6 as moderate, and 12 with severe CD activity. Although patients with mild (odds ratio, 1.14; 95% CI, 0.40–3.20) and moderate to severe (odds ratio, 1.97; 95% CI, 0.62–6.35) activity were at increased risk of disease recurrence, the differences were not statistically significant. Patients with mild (hazard ratio, 0.97; 95% CI, 0.50–1.91) and moderate to severe (hazard ratio, 1.29; 95% CI, 0.65–2.55) disease activity at margins did not have significantly different time-to- recurrence compared with those without disease activity. Conclusions.—Our study suggests CD activity at resec- tion margins is not significantly associated with postoper- ative CD recurrence. (Arch Pathol Lab Med. 2019;143:505–509; doi: 10.5858/ arpa.2018-0011-OA) M ore than 25% of all patients with Crohn disease (CD) require surgical resection in their lifetime. 1 In a large cohort study of adults with CD, surgery was reported in half of all cases within 10 years after diagnosis, with postoper- ative CD recurrence (defined as histologic, endoscopic, radiographic, clinical, or surgical) occurring in 33% to 40% of patients at 5 years, 44% to 55% at 10 years, and 70% at 20 years. 2 Because of these high postoperative CD recurrence rates, predictors of CD recurrence based on histologic, clinical, endoscopic, and surgical features of CD patients are of great interest and have been the subject of several studies. There are conflicting data regarding the prognostic value of CD histologic features in bowel resection specimens. In the early 1980s, Karesen and colleagues 3 reported that the presence of microscopic CD at surgical resection margins was associated with increased postoperative CD recurrence, and a wide resection with frozen section evaluation of the resection margins was recommended. A study by Wolff et al 4 drew a similar conclusion and also recommended that frozen sections be performed on grossly normal CD resection margins to rule out microscopic disease. In 1993, Heimann et al 5 found that patients with severe CD who needed multiple resections with anastomosis that had microscopic inflammation at the resection margins were at high risk for early symptomatic disease recurrence. How- ever, other studies suggested the presence of microscopic CD at surgical resection margins was not associated with postoperative CD recurrence. 6,7 Kotanagi et al 8 found that recurrence of CD at the anastomotic site did not correlate with any histologic features at the resection margin, including pyloric gland metaplasia, fibrosis, cryptitis, crypt abscesses, ulcers, granulomas, or transmural inflammation. Finally, a randomized controlled trial of 131 patients who had resections between 1986 and 1993 showed no significant difference in recurrence rates between wide- margin and limited-margin resection or disease activity at time of resection. 9 Accepted for publication June 8, 2018. Published online November 16, 2018. From the Department of Pathology (Drs Setoodeh and Gopal) and the Division of Digestive and Liver Diseases (Drs Singal and Ahmed), UT Southwestern Medical Center, Dallas, Texas; the Department of Pathology, Mercy Medical Center, Baltimore, Maryland (Dr Liu); the Department of Pathology, University of Iowa Healthcare, Iowa City (Dr Boukhar); the Department of Pathology (Dr Westerhoff) and the Division of Gastroenterology and Hepatology (Dr Waljee), Univer- sity of Michigan Health System, Ann Arbor; and VA Center for Clinical Management Research, VA Ann Arbor Health Care System, Ann Arbor, Michigan (Dr Waljee). Dr Ahmed is a paid speaker for Abbvie Inc. The other authors have no relevant financial interest in the products or companies described in this article. Presented as a poster at the United States and Canadian Academy of Pathology annual meeting; Seattle, Washington; March 15, 2016. Corresponding author: Purva Gopal, MD, MS, Department of Pathology, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9072 (email: Purva.gopal@utsouthwestern.edu). Arch Pathol Lab Med—Vol 143, April 2019 Resection Margins in Crohn Disease—Setoodeh et al 505